The ultimate objective of this research project will be the development and commercialization of a low cost, reliable and widely available point-of-care testing device for screening, diagnosis and management of disease in human patients. The proposed technique, submillimeter photoacoustic spectrometry of human breath, will initially be used to identify and quantify molecular bio-marker profiles that simulate the discrimination of metabolic products in patients with symptoms for a small number of selected diseases including asthma, bronchiectasis, interstitial lung disease. A major advantage of the proposed technique is that it is non-invasive, and highly selective based on state-specific detection of molecular finger print profiles characteristic of the specific diseases. This will be achieved by application of recently availability of intense and highly monochromatic backward-wave oscillators spectroscopic sources (10-100 mWatt power, 3x10/-8 cm/-1 linewidth). Such capabilities will be incorporated in our device design, and exploited to identify and measure the characteristic frequency signatures of selected molecular markers including nitric oxide, carbon monoxide, and ammonia with ppb or better sensitivity necessary for effective medical application. The proposed work will demonstrate the feasibility and practicability of the proposed technique for the diagnosis and management of the selected diseases. We propose to carry out the following tasks during this Phase I STTR: 1) Assemble initial bench scale assembly and setup. 2) Establish procedures for calibration and verification of molecular markers. 3) Develop procedures for preparation and delivery of specified concentrations of marker molecules in sample chamber of device. 4) Demonstrate ppb detection levels for single specific biomarker molecules. 5) Demonstrate simultaneous ppb detection of simulant mixtures of different bio-markers. 6) Conceptually design small footprint Phase II prototype. Commercialization: The proposed studies will prepare the way for the subsequent simplification and miniaturization of the initial instrumental design in Phases II and III. During this development, we will work with medical device manufacturers to assist in manufacturing, FDA approval, and marketing. Further market segments for commercialization will be explored for its wider and more general medical use.